A facility has been established for the high precision measurement of breath CO2 by mass spectrometry with the purpose of detecting the oxidative utilization of 13C-labeled substrates in human subjects. Using cholyl-l-l3-C-glycine, l,l-13C-dimethyl-aminopyrine, and the fats tri-l-13C-octanoin, tri-l-l3C-olein, and l-13C-palmitate, clinical 13CO2 breath tests have been performed to measure bile salt deconjugation, hepatic microsomal function, and fat malabsorption in populations where 14C cannot be used. In the coming year, the following clinical studies will be initiated using these substrates: the incidence of bile salt malabsorption in malnourished Guatemalian children with chronic diarrhea, the change in hepatic function in subjects recovering from alcoholic cirrhosis, and the identification of the cause of fat malabsorption in children with steatorrhea (pancreatic insufficiency, mucosal damage, or intraluminal defect). Three new 13C substrates will be tested. These include 13C-methacetin and l-13C-ethyl-phenacetin which will be compared to aminopyrine for the assessment of hepatic microsomal function. The third, 13C-lactose, will be validated against its 14C analog for the detection of lactose malabsorption and then applied in a study of the development of intestinal lactose catabolism in newborns. Two recent instrumental developments will undergo clinical testing. An automated controller that performs the purification and analysis of breath 13CO2 will be installed. Estimates of the cost and speed of doing 13C breath tests will be made in an effort to assertain the practicality of performing 13C breath tests on a routine clinical basis. The second instrument is a combustion furnace that will be used in converting fecal material to CO2 for isotopic analysis. This system will be used in measuring excretion of malabsorbed cholyl-l-13C-glycine and 13C-lactose.